Astrocyte activation is suppressed in both normal and injured brain by FGF signaling

Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):E2987-95. doi: 10.1073/pnas.1320401111. Epub 2014 Jul 7.


In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss- and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets.

Keywords: astrogliosis; brain damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology*
  • Brain / metabolism*
  • Brain / pathology*
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology*
  • Cerebral Cortex / pathology
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Fibroblast Growth Factors / metabolism*
  • Genotype
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / metabolism
  • Gliosis / pathology
  • Mice
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction*


  • Glial Fibrillary Acidic Protein
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors